Synaptogenic activity of the axon guidance molecule Robo2 underlies hippocampal circuit function
Heike Blockus,
Sebi V. Rolotti,
Miklos Szoboszlay,
Eugénie Peze-Heidsieck,
Tiffany Ming,
Anna Schroeder,
Nuno Apostolo,
Kristel M. Vennekens,
Phinikoula S. Katsamba,
Fabiana Bahna,
Seetha Mannepalli,
Goran Ahlsen,
Barry Honig,
Lawrence Shapiro,
Joris de Wit,
Attila Losonczy,
Franck Polleux
Affiliations
Heike Blockus
Department of Neuroscience, Columbia University, New York, NY 10027, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA
Sebi V. Rolotti
Department of Neuroscience, Columbia University, New York, NY 10027, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA
Miklos Szoboszlay
Department of Neuroscience, Columbia University, New York, NY 10027, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA
Eugénie Peze-Heidsieck
Department of Neuroscience, Columbia University, New York, NY 10027, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA
Tiffany Ming
Department of Neuroscience, Columbia University, New York, NY 10027, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA
Anna Schroeder
VIB Center for Brain and Disease Research, Herestraat 49, 3000 Leuven, Belgium; Department of Neurosciences, KU Leuven, Herestraat 49, 3000 Leuven, Belgium
Nuno Apostolo
VIB Center for Brain and Disease Research, Herestraat 49, 3000 Leuven, Belgium; Department of Neurosciences, KU Leuven, Herestraat 49, 3000 Leuven, Belgium
Kristel M. Vennekens
VIB Center for Brain and Disease Research, Herestraat 49, 3000 Leuven, Belgium; Department of Neurosciences, KU Leuven, Herestraat 49, 3000 Leuven, Belgium
Phinikoula S. Katsamba
Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA
Fabiana Bahna
Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA
Seetha Mannepalli
Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA
Goran Ahlsen
Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA
Barry Honig
Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Department of Medicine, Columbia University, New York, NY 10032, USA
Lawrence Shapiro
Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA
Joris de Wit
VIB Center for Brain and Disease Research, Herestraat 49, 3000 Leuven, Belgium; Department of Neurosciences, KU Leuven, Herestraat 49, 3000 Leuven, Belgium
Attila Losonczy
Department of Neuroscience, Columbia University, New York, NY 10027, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Kavli Institute for Brain Science, Columbia University, New York, NY 10027, USA; Corresponding author
Franck Polleux
Department of Neuroscience, Columbia University, New York, NY 10027, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Kavli Institute for Brain Science, Columbia University, New York, NY 10027, USA; Corresponding author
Summary: Synaptic connectivity within adult circuits exhibits a remarkable degree of cellular and subcellular specificity. We report that the axon guidance receptor Robo2 plays a role in establishing synaptic specificity in hippocampal CA1. In vivo, Robo2 is present and required postsynaptically in CA1 pyramidal neurons (PNs) for the formation of excitatory (E) but not inhibitory (I) synapses, specifically in proximal but not distal dendritic compartments. In vitro approaches show that the synaptogenic activity of Robo2 involves a trans-synaptic interaction with presynaptic Neurexins, as well as binding to its canonical extracellular ligand Slit. In vivo 2-photon Ca2+ imaging of CA1 PNs during spatial navigation in awake behaving mice shows that preventing Robo2-dependent excitatory synapse formation cell autonomously during development alters place cell properties of adult CA1 PNs. Our results identify a trans-synaptic complex linking the establishment of synaptic specificity to circuit function.
